Birgitta Versluijs

10 1 Principles of HCT General introduction The bone marrow is the organ where blood cells are generated from hematopoietic stem cells. Allogeneic Hematopoietic Cell Transplantation (HCT) refers to the transfer of these hematopoietic stem cells from one individual to another, to obtain lifelong engraftment of the administered stem cells and thus guarantee the production of healthy donor de- rived blood cells. The cellular components of blood (erythrocytes, thrombocytes and leucocytes) are essential for oxygen supply, coagulation and immunity. HCT is a poten- tially life-saving procedure for selected patients with malignant diseases (leukemia, lym- phoma) and non-malignant diseases (bone marrow failure syndromes, hemoglobinopa- thies, primary immune deficiencies, inborn errors of metabolism). In the Netherlands, a total of 350-400 allogeneic HCTs are performed annually, of which approximately 80-90 in children. 1 Principles of hematopoietic cell transplantation Donor selection is based primarily on Human Leucocyte Antigen (HLA) match. The HLA system is the most polymorphic genetic system in humans. The biological role of the HLA class I and class II molecules is to present processed peptide antigens on the outer part of body cells, leading to a highly specific signature. In HCT, HLA-A, -B, -C, -DR, -DQ and -DP are clinically important. The immune system differentiates “self-cells” from “non-self” via HLA. In HCT a donor-derived immune system will develop in a “non-self” environment, so HLA-matching is important to avoid immune mediated com- plications. In general, better HLA-matching leads to a decreased risk of graft rejection, as well as a lower incidence of Graft versus Host Disease (GvHD), an inflammatory disease caused by donor immune cells attacking normal recipient tissue. HLA inheritance fol- lows Mendelian rules, so a sibling has only 25% chance of being HLA identical. Expan- sion of the donor pool, in order to be able to offer HCT to more patients, was achieved by the establishment of international bone marrow donor registries and cord blood banks. Over time the use of unrelated donors has increased. Donor source can be either Bone Marrow (BM), Peripheral Blood Stem Cells (PBSC) or Cord Blood (CB). Every option has its own advantages and disadvantages. BM harvesting requires general anaesthesia of the donor, but the product contains useful stromal cells besides the hematopoietic stem cells. PBSC are mobilized using granulocyte stimulating factors with potential side effects for the donors. Very high stem cell doses can be ob- tained, but there is an increased risk for chronic GvHD. It thus never became popular in pediatric HCT. Cord blood units are harvested direct post-partum, without any risk for the donor. A great advantage is the less stringent HLA matching criteria, the down side